Regional administration of natural killer cells in a rat hepatic metastasis model results in better tumor infiltration and anti-tumor response than systemic administration.
A syngeneic rat liver metastasis model, the CC531 colon carcinoma cell line in Wag rats, was used to study the homing properties and anti-tumor effects of adoptively transferred, interleukin-2 (IL-2)-activated, cultured natural killer (A-NK) cells. To identify the route of administration that gives the highest tumor infiltration, 1.5 x 10(8) A-NK cells were dyed with fluorescent rhodamine and injected via 4 different routes into rats, bearing subcapsularly induced (day 10) liver metastases. The routes chosen were: jugular vein, portal vein, hepatic artery and directly into the peritoneal cavity (i.p). The rats were sacrificed 20 hr after administration of A-NK cells. The highest (p < 0.05) infiltration of tumors by A-NK cells was found both at the tumor border and in the tumor center after injection via the hepatic artery: 65 +/- 7 A-NK cells/mm2 at the tumor border and 26 +/- 14 A-NK cells/mm2 in the center of the tumor (jugular vein infusion: 32 +/- 10 and 9 +/- 5 A-NK cells/mm2, respectively; portal vein infusion: 36 +/- 13 and 7 +/- 4 A-NK cells/mm2, respectively). No A-NK cells were detected in the liver after i.p. injection. Rats bearing day 5 tumors were injected with 1.5 x 10(8) A-NK cells via the hepatic artery or via the jugular vein (n = 5 and n = 6 respectively). Regional administration of A-NK cells via the hepatic artery resulted in a significant (p < 0.05) lower weight (35 +/- 23 mg) of tumors than did systemic administration (70 +/- 10 mg). Our results suggest that both the level of tumor infiltration by adoptively transferred A-NK cells and the therapeutic outcome depend on the route of administration.
Hagenaars
M
M
Department of Surgery, Leiden University Hospital, The Netherlands.
Ensink
N G
NG
Koelemij
R
R
Basse
P H
PH
Eggermont
A M
AM
van de Velde
C J
CJ
Fleuren
G J
GJ
Kuppen
P J
PJ
D000818:Animals; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar